Dynamic changes in peripheral blood lymphocyte subset counts and functions in patients with diffuse large B cell lymphoma during chemotherapy

Hou, Hongyan; Luo, Ying; Tang, Guoqing; Zhang, Bo; Ouyang, Renren; Wang, Ting; Huang, Min; Wu, Shiji; Li, Dengju

doi:10.1186/s12935-021-01978-w

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…The origin and functional mechanism of ncMO2, cDC2 and cDC3, which are DHL-related monocytes subsets, need to be further studied. Furthermore, the NK cell ratio was significantly elevated in DHL and DLBCL groups, which is different from the previous report that NK cells are subjected to exhaustion and at the low level in newly diagnosed DLBCL patients [ 37 ], further investigation should be done in the next stage with dynamic blood samples.…”

Section: Discussioncontrasting

confidence: 97%

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

Lei

et al. 2023

BMC Cancer

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Background Double-hit or Triple-hit lymphoma (DHL/THL) is a subset of high-grade B cell lymphoma harboring rearrangements of MYC and BCL2 and/or BCL6, and usually associate with aggressive profile, while current therapies tend to provide poor clinical outcomes and eventually relapsed. Further explorations of DHL at cellular and molecular levels are in demand to offer guidance for clinical activity. Methods We collected the peripheral blood of DHL patients and diffused large B cell lymphoma (DLBCL) patients from single institute and converted them into PBMC samples. Mass cytometry was then performed to characterize these samples by 42 antibody markers with samples of healthy people as control. We divided the immune cell subtypes based on the expression profile of surface antigens, and the proportion of each cell subtype was also analyzed. By comparing the data of the DLBCL group and the healthy group, we figured out the distinguished immune cell subtypes of DHL patients according to their abundance and marker expression level. We further analyzed the heterogeneity of DHL samples by pairwise comparison based on clinical characteristics. Results We found double-positive T cells (DPT) cells were in a significantly high percentage in DHL patients, whereas the ratio of double-negative T cells (DNT) was largely reduced in patients. Besides, CD38 was uniquely expressed at a high level on some naïve B cells of DHL patients, which could be a marker for the diagnosis of DHL (distinguishing from DLBCL), or even be a drug target for the treatment of DHL. In addition, we illustrated the heterogeneity of DHL patients in terms of immune cell landscape, and highlighted TP53 as a major factor that contributes to the heterogeneity of the T cells profile. Conclusion Our study demonstrated the distinct peripheral immune cell profile of DHL patients by contrast to DLBCL patients and healthy people, as well as the heterogeneity within the DHL group, which could provide valuable guidance for the diagnosis and treatment of DHL.

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Section: Discussioncontrasting

confidence: 97%

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

Lei

et al. 2023

BMC Cancer

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“…The results indicated that NHL patients had immune-function deficiencies in their peripheral blood, suggesting an immune defect. In agreement with previous reports, the study revealed that NHL patients had significantly decreased peripheral immune-cell percentages compared with the healthy controls [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. When the immune system cannot function optimally, T and B cells fail to detect or destroy tumor cells [ 18 , 34 ].…”

Section: Discussionsupporting

confidence: 92%

PD-L1 Is Involved in the Development of Non-Hodgkin’s Lymphoma by Mediating Circulating Lymphocyte Apoptosis

Saber

2023

Vaccines

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Lymphocyte apoptosis plays a crucial role in tumor-induced immunosuppression. Programmed death ligand-1 (PD-L1) blocks lymphocyte activation via its receptor, PD-1. However, PD-L1/PD-1 expression and its role in enhancing immune suppression in non-Hodgkin lymphoma (NHL) have not been identified. The purpose of the study was to assess PD-L1/PD-1 expression in circulating lymphocytes in NHL and its role in immunosuppression. Twenty newly diagnosed NHL patients and twenty normal volunteers were enrolled in the study. PD-L1/PD-1 expression in circulating lymphocytes and the apoptosis of lymphocyte subsets were assessed using flow cytometry. The findings revealed that the PD-L1 expression in circulating CD3+, CD3+CD4+, CD3+CD8+, and CD20+ lymphocytes were dramatically upregulated in NHL patients (p < 0.001), whereas peripheral lymphocytes expressed low levels of PD-1. Compared with normal volunteers, a significant increase in lymphocyte apoptosis was revealed by annexin-V binding on T and B lymphocytes (p < 0.001). Peripheral lymphocytes expressing PD-L1 were four times more vulnerable to apoptosis than those expressing PD-1. Our findings imply that PD-L1 upregulation contributes to NHL development by promoting circulating lymphocyte apoptosis. This research adds to our understanding of the function of the PD-L1/PD-1 pathway in tumor evasion, establishing a novel therapeutic target in NHL. The results offer additional evidence for the immunomodulatory role of PD-L1 in circulating lymphocytes, providing a rationale for further investigations into immunological dysfunctions resulting from NHL. PD-L1+ lymphocytes could be employed as a biomarker to assess the effectiveness of immune systems and predict illness in patients with NHL.

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“…A similar trend was also found in anti‐ALK AAb of patients with ALCL 10 . Relapsed patients are resistant to rituximab and the function of B cells is weakly inhibited, which thus leads to increased levels of AAbs 36 …”

Section: Discussionsupporting

confidence: 71%

“…10 Relapsed patients are resistant to rituximab and the function of B cells is weakly inhibited, which thus leads to increased levels of AAbs. 36 Four AAbs (CREB1, N4BP1, DEAF1, and UBAP2) were associated with superior prognosis, and might play a role in relieving drug resistance through NF-κB signaling pathways. Cyclic adenosine monophosphate response element-binding protein 1 (CREB1) is a nuclear transcription factor that plays a crucial role in cell differentiation, F I G U R E 6 Prognostic value of CREB1 and N4BP1 proteins and mRNA in the IHC cohort (n = 55; 100�) and four DLBCL GEO data sets (n = 1598).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic autoantibodies in diffuse large B‐cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone via a high‐throughput antigen microarray

Dai,

Chen,

Tan

et al. 2023

Cancer

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BackgroundR‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL). However, 20%–40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand.MethodsBaseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high‐density antigen microarray (∼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL‐focused microarray, comparative results based on event‐free survival at 24 months (EFS24) and lasso Cox regression models of progression‐free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme‐linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two‐AAb‐based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598).ResultsFour AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p < .05) and superior PFS and OS (p < .05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R‐CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p < .05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p < .05).ConclusionsThis study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL.

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Dynamic changes in peripheral blood lymphocyte subset counts and functions in patients with diffuse large B cell lymphoma during chemotherapy

Cited by 7 publications

References 27 publications

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

PD-L1 Is Involved in the Development of Non-Hodgkin’s Lymphoma by Mediating Circulating Lymphocyte Apoptosis

Identification of novel prognostic autoantibodies in diffuse large B‐cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone via a high‐throughput antigen microarray

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